Chordoma of the Sacrum and Vertebral Bodies

Review Article Chordoma of the Sacrum and Vertebral Bodies

Abstract Daniel M. Sciubba, MD Chordomas are relatively rare tumors of bone. These primary Jennifer J. Cheng, MD malignant lesions occur throughout the spinal column and often show advanced growth at the time of diagnosis. Because such Rory J. Petteys, BS tumors are minimally responsive to radiation and chemotherapy, Kristy L. Weber, MD surgical resection is the mainstay of treatment. Patient survival and Deborah A. Frassica, MD local control are associated with the ability to achieve wide surgical Ziya L. Gokaslan, MD margins during excision. However, surgical morbidity may be substantial given the propensity for chordomas to abut or surround neural, vascular, and visceral structures. Thus, early recognition is essential, and treatment by a multidisciplinary team is ideal.

hordomas are relatively rare, ple.2 These tumors affect men nearly Cslow-growing, primary malig- twice as frequently as women, and nant bone tumors. They are thought they are most commonly diagnosed Dr. Sciubba is Assistant Professor of to arise from notochordal remnants in middle-aged persons.2 Although Neurosurgery, Oncology, and and thus they occur along the mid- chordoma can occur in the pediatric Orthopaedic Surgery, Department of Neurological Surgery, Johns line from the skull base to the population, particularly at the skull Hopkins University, Baltimore, MD. sacrum. Because of their indolent base, this is rare and accounts for Dr. Cheng is Resident Physician, and low-grade nature, chordomas <5% of all chordomas.2 The median Department of Neurological Surgery, are typically diagnosed at a late stage age at diagnosis is 58.5 years, and Johns Hopkins University. 2 Mr. Petteys is Resident Physician, and therefore, often cause significant the incidence increases with age. Department of Neurological Surgery, damage through local bone destruc- Chordomas occur only one fourth as Georgetown University, Washington, tion and compromise of neurologic frequently in blacks as in whites.2 DC. Dr. Weber is Professor of structures. The goal of treatment is Chordomas are found in the midline Orthopaedic Surgery, Department of Orthopaedic Surgery, Johns Hopkins to achieve surgical en bloc excision of the neuraxis, where they arise from University. Dr. Frassica is Associate with tumor-free margins to maximize intraosseous notochordal remnants Professor of Radiation Oncology local tumor control and overall sur- within spinal segments from the clivus and Oncology, Department of Radiation Oncology, Johns Hopkins vival. Radiation therapy is often used to the coccyx. The anatomic distribu- University. Dr. Gokaslan is Professor postoperatively when tumor-free tion has been commonly reported to be of Neurosurgery, Oncology, and margins cannot be achieved. Progno- approximately 50% sacrococcygeal and Orthopaedic Surgery, Department of sis in terms of both overall survival Neurological Surgery, Johns 35% sphenooccipital, with15% occur- and prevention of local recurrence is Hopkins University. ring in the mobile spine, although this highly dependent on the adequacy of Reprint requests: Dr. Sciubba, distribution varies by case series.3 In initial surgical margins. Department of Neurological Surgery, the largest published series to date Johns Hopkins University, 600 North (400 cases), McMaster et al2 re- Wolfe Street, Meyer 8-161, Baltimore, MD 21237. Epidemiology ported that chordomas appeared in sacral, sphenooccipital, and spinal J Am Acad Orthop Surg 2009;17: 708-717 Chordomas comprise 1% to 4% of locations with approximately equal all primary bone tumors.1 The age- frequency. Boriani et al4 observed Copyright 2009 by the American Academy of Orthopaedic Surgeons. adjusted incidence rate in the general that chordomas that affect the mo- population is 0.8 per 1,000,000 peo- bile spine involve the lumbar spine

708 Journal of the American Academy of Orthopaedic Surgeons Daniel M. Sciubba, MD, et al

Figure 1 Figure 2

T1-weighted (A) and gadolinium-enhanced T1-weighted (B) sagittal MRI scans demonstrating a cervical chordoma involving C1-C2 (arrow) and the lower clivus, with close involvement of skull base structures. The arrowhead indicates wrapping around the brainstem. T2-weighted sagittal MRI scan demonstrating a sacral chordoma most frequently (57% to 66%), fol- sory deficits, bowel and bladder in- abutting the rectum (arrow). lowed by the cervical spine (24% to continence, and sexual dysfunction. 29%) and the thoracic spine (10% Regional extension dictates symp- to 13.5%). Chordomas are the tomatology, including symptoms not toms in reported series ranges from 4 most common primary bone tumors directly attributable to spinal cord or to 40 months.4,5 4 found in the mobile spine and the nerve root compromise. Chordomas 5 sacrum. involving the cervical region (Figure Advanced Imaging 1) may obstruct the airway, give rise Features Presentation to a retropharyngeal mass, or cause dysphagia, dysphonia, or Horner Chordoma classically appears as an Although the presentation of these syndrome.6 In the sacral region (Fig- osteolytic lesion centered in the mid- lesions varies by location, pain is re- ure 2), presacral extension of chor- line and in association with a large ported to be the most common pre- domas can lead to rectal dysfunction, soft-tissue mass. Osteosclerotic areas senting symptom regardless of loca- including obstipation, constipation, or areas of mixed osteolytic and os- tion, in particular, pain with a tenesmus, and hemorrhoids, as well teosclerotic bone destruction may be gradual and insidious onset.3,4 Chor- as gluteal masses or masses that are seen on CT scan. Amorphous intra- domas often encroach on the spinal palpable on rectal examination.7 Be- tumoral calcification can be detected canal, and they may cause compres- cause of their slow growth rate and on CT imaging in 30% to 90% of sion of the spinal cord, cauda the often nonspecific nature of their cases.8,9 In >50% of cases, a higher- equina, or nerve roots. This is re- symptoms, chordomas often evade attenuation fibrous pseudocapsule flected in a wide range of neurologic diagnosis until late in the disease can be seen surrounding the lower- symptoms, including weakness, sen- course.7 The mean duration of symp- attenuation soft-tissue mass.8 Com-

Dr. Sciubba or a member of his immediate family has received research or institutional support from AO, DePuy, and Medtronic Sofamor Danek. Dr. Weber or a member of her immediate family serves as a board member, owner, or committee member of the American Orthopaedic Association, Orthopaedic Research and Education Foundation, Orthopaedic Research Society, Musculoskeletal Tumor Society, and Ruth Jackson Orthopaedic Society. Dr. Gokaslan or a member of his immediate family has received research or institutional support from AO North America and Medtronic, has stock or stock options held in US Spine and Spinal Kinetics, and has received nonincome support (such as equipment or services), commercially derived honoraria, or other non–research-related funding (such as paid travel) from AO North America. None of the following authors or a member of their immediate families has received anything of value from or owns stock in a commercial company or institution related directly or indirectly to the subject of this article: Dr. Cheng, Mr. Petteys, and Dr. Frassica.

November 2009, Vol 17, No 11 709 Chordoma of the Sacrum and Vertebral Bodies

Figure 3 round, and darkly staining, and they because of their lytic appearance, but display a mild to moderate amount chordomas demonstrate positive of nuclear pleomorphism, with few scintigraphy.15 Osteomyelitis and mitotic figures.10 Mucin is abundant lymphoma are also difficult to distin- both intracellularly and extracellu- guish radiographically, but they can larly in the surrounding myxoid be distinguished from one another stroma.8-10 Necrotic areas are infre- because of their distinct clinical quently seen within chordomas; ar- courses.15 Benign notochordal rests eas of calcification, hemorrhage, and do not display the bony destruction, resultant hemosiderin deposition are cortical disruption, or associated more common.10 The mucinous soft-tissue masses seen in chordo- Photomicrograph of a chordoma stroma may contain prominent sar- mas.16 Clinically, they are indolent (hematoxylin-eosin, original comatous elements, whether fibrous, and usually asymptomatic.16 magniﬁcation ×400). Note the vacuolated physaliphorous (“soap chondroid, or osteoid, in dedifferen- Chordomas can be distinguished 8-10,12 bubble”) cells, a pathognomonic tiated chordomas. These dediffer- from chondrosarcoma and meta- feature of these tumors. entiated chordomas are comparatively static tumors on radiographic evalu- aggressive, tend to exhibit high-grade ation because chordomas lack the as- behavior, and carry a poor prog- sociated soft-tissue mass.15 Other 12 pared with muscle, chordomas range nosis. In the well-described vari- primary sacral tumors include be- from isointense to hypointense on ant, chondroid chordoma, areas of nign lesions (eg, giant cell tumor, an- T1-weighted MRI scans and are hy- bland-appearing hyaline cartilage eurysmal bone cyst, osteoid osteoma, 9 perintense on T2-weighted images make up a substantial component of osteoblastoma, hemangioma, nerve 10,11 (Figures 1 and 2). the specimen. sheath tumor) and malignant lesions Benign notochordal cell tumors, Chordomas are well-defined ex- (eg, Ewing sarcoma, primitive neuro- also known as notochordal rests, are tramedullary masses that may be ectodermal tumor, osteosarcoma, seen to compress and sometimes to benign intraosseous lesions that of- Paget’s sarcoma, multiple myeloma, encase adjacent neurovascular struc- ten are mistaken for chordomas. plasmacytoma).9 The differential di- tures.10 These tumors commonly in- The anatomic distribution of noto- agnosis for primary vertebral lesions vade the intervertebral disk space as chordal rests is the same as that includes all of these entities as well they extend between adjacent verte- of chordomas, and it has been as teratoma and dermoid.17 Myxo- bral bodies.11 Chordomas may ap- suggested that these lesions may papillary ependymomas, which are pear heterogeneous on T2-weighted be precursors of chordomas.13 Be- lesions that arise from the filum ter- MRI scans; they have internal hy- nign notochordal rests are made up minale, are also occasionally mis- pointense foci on T1-weighted im- of sheets of vacuolated cells mixed taken for chordomas.18 ages because of intralesional cal- with less vacuolated cells. It is impor- Immunohistochemical analysis is one cification, cystic changes, and tant to note that benign notochordal method of distinguishing chordomas hemorrhage.10 They display promi- rests lack the surrounding myxoid from other lesions that are histologically nent contrast enhancement on both stroma characteristic of chordomas similar, including choroid meningioma, CT and MRI scans. and have no mitotic figures or ne- chondroma, chondrosarcoma, mela- crotic areas.14 noma, and metastatic adenocarcinoma. Histologic Features Most chordomas display S-100 immu- Differential Diagnosis noreactivity, thus distinguishing them Chordomas consist of lobulated tumor from metastatic adenocarcinoma and cell nests separated by fibrous septae, Although chordomas are the most meningioma, as well as epithelial mem- often within an overlying pseudocap- frequently occurring primary malig- brane antigen immunoreactivity, thus sule. Sheets or elongated cords of clear nant bone tumor in both the sacrum5 distinguishing them from chondroma, cells with multiple intracytoplasmic and the mobile spine,4 metastatic le- chondrosarcoma, and melanoma.10 vacuoles, so-called physaliphorous sions and multiple myeloma make up Positive cytokeratin CAM 5.2 immu- (“soap bubble”) cells, are a pathogno- the overwhelming majority of sacral noreactivity is a highly sensitive but monic feature of these tumors8-10 and spinal neoplasms.9 Chordomas nonspecific means of detecting chor- (Figure 3). The nuclei are small, may be confused with plasmacytoma doma.10

710 Journal of the American Academy of Orthopaedic Surgeons Daniel M. Sciubba, MD, et al

Staging Figure 4

As with other neoplastic processes, staging of suspected chordomas is conducted in two parts: oncologic and surgical. Oncologic staging requires a complete workup, including advanced imaging (ie, MRI, CT), laboratory studies, and biopsy. MRI of the primary site is important to determine the local extent of the chordoma. A thorough survey for signs of local or systemic metastasis should be performed via CT with in- travenous contrast of the chest, ab- domen, and pelvis. When the primary tumor appears to be at an advanced stage, a more thorough metastatic workup with whole-body positron emission tomography or bone scan should be performed. Ad- ditionally, a tissue-proven diagnosis is important to optimize treatment strategies and to distinguish chor- Weinstein-Boriani-Biagini surgical staging system used to classify tumors of doma from mimicking lesions.11 Be- mobile spine segments. Tumor extent is speciﬁed using a clock-face cause chordomas have the ability to radiating zone system. (Adapted with permission from Boriani S, Weinstein JN, Biagini R: Primary bone tumors of the spine: Terminology and surgical seed along biopsy tracts, all biopsy staging. Spine [Phila Pa 1976] 1997;22:1036-1044.) tracts should be carefully marked so that they can be removed during sub- sequent surgery. Care must be taken ses.19,20 Chordomas generally fall into structures is recommended. to ensure that biopsy needles do not stage IB at the time of diagnosis, that The Weinstein-Boriani-Biagini clas- transgress other body cavities. Spe- is, low-grade malignant tumors that sification was proposed as a surgical cifically, transrectal biopsies should have invaded the paravertebral com- staging system specific to tumors of be avoided so as to prevent spread of partment.7,23 Stage IA tumors are mobile spine segments in which tu- chordoma into the rectum.3 confined within the vertebral body. mor extent is specified using a clock- The Enneking staging system was Advancements in imaging techniques face radiating zone system.25 This al- developed to describe the biologic have improved our ability to detect lows a three-dimensional description behavior of benign and malignant chordomas at an earlier stage.24 A tu- of tumor extent in terms of its ante- primary bone neoplasms as well as mor is classified as stage III in the rior, posterior, right, left, circumfer- to determine the extent of surgery re- presence of distant metastasis, with ential, and longitudinal dimensions25 quired for excision (eg, intralesional, subtypes A and B used to delineate (Figure 4). Although this system has marginal, wide, or radical).19,20 This whether the metastasis is intra- or not been validated, it can be useful in system is useful in surgical planning extracompartmental. Based on the surgical planning. Its utility has been for long-bone lesions, and it has been Enneking staging system, most chor- demonstrated in its application to gi- applied to spinal neoplasms in some domas (stage I, A and B) should be ant cell tumors of the spine.21 studies.21,22 Tumors are classified treated with en bloc excision, with Chan et al26 recently demonstrated based on histologic grade (stage I the goal of obtaining wide tumor- substantial inter- and intraobserver through III), anatomic site (intra- free margins.19,20 In the presence of reliability with the Enneking and compartmental [subtype A], extra- metastatic or multifocal disease, a Weinstein-Boriani-Biagini classifica- compartmental [subtype B]), and more limited intralesional resection tion systems for staging and guiding presence or absence of metasta- to relieve compression of neural treatment of primary spine tumors.

November 2009, Vol 17, No 11 711 Chordoma of the Sacrum and Vertebral Bodies

Figure 5 In general, ipsilateral resection of sacral nerve roots leads to ipsilateral motor and sensory deficits corre- sponding to the levels sacrificed; however, bowel and bladder function are usually entirely preserved.28 Low sacral amputations commonly result in complete preservation of sphincter function,28 although perineal numb- ness and sexual dysfunction are common.23 Midsacral amputations result in a variable degree of functional loss. Most patients are left with saddle anesthesia and reduced sphincter control but retain intact motor function.29 Preservation of at least one S3 root A, Intraoperative PA photograph taken following midsacral amputation in the will result in normal bowel and blad- 28 patient seen in Figure 2. A large soft-tissue defect remains next to the der function in most patients. Lim- posterior rectum (black arrow). The distal roots were ligated and sectioned ited functional urinary and fecal con- with the specimen, and the salvaged S3 roots are visible bilaterally (white tinence may be preserved when at arrows). B, Specimen following en bloc removal. least one S2 nerve root is spared, although most patients will have ab- normal sphincter function.23 High The goal with the latter staging sys- strate a direct correlation between sacral amputation and total sacrec- tem is to assist with surgical plan- the extent of surgical resection and tomy with resection of the S1 nerve ning and to provide a unified means the length of recurrence-free surviv- root frequently results in postopera- of describing spinal tumors so that 27 al. tive motor deficits, particularly in data can be more easily compared Sacral chordoma resection involves ankle plantar flexion. This can im- within the field.21,25 The intent with amputation of a portion of the distal pair the patient’s ability to ambulate surgical staging is to identify the ex- sacrum or removal of the entire without external support, even if tent of local invasion of the tumor sacrum (Figure 5). A portion of the only temporarily.23 Patients undergo- and to determine which structures adjacent bony pelvis may also be re- ing high sacral amputation or total (ie, vessels, nerves, viscera, paraver- moved to achieve an adequate mar- sacrectomy usually experience com- tebral soft tissue) can be sacrificed to gin. These procedures often involve plete loss of sphincter control as well achieve en bloc resection. When criti- the intentional sacrifice of one or as saddle anesthesia and sexual dys- cal structures cannot be removed more sacral nerve roots to achieve function.30 with the tumor specimen, an intrale- wide resection of the lesion. This Surgical management of sacral chor- sional excision may be necessary. may result in motor, sensory, sphinc- domas is challenging because of the ter, or sexual dysfunction. The resec- complex regional anatomy, the often Management tions can be classified based on the advanced stage of tumor growth, and location of the highest segment re- the proximity to and encroachment on Surgery remains the mainstay of moved or according to the highest surrounding tissues. Accordingly, it is management of chordomas. How- level of nerve root sacrificed. We appropriate to bring together a multi- ever, adjuvant therapies are currently herein define sacral amputations as disciplinary surgical team whose mem- under investigation. Given the low- low (sacrifice of at least one S4 nerve bers may include specialists in surgical grade nature of these lesions, wide en root or any level below), middle (sac- oncology, neurosurgery, orthopaedic bloc excision is mandatory for cura- rifice of at least one S3 nerve root), surgery, vascular surgery, and plastic tive treatment. The importance of or high (sacrifice of at least one S2 surgery. Adequate exposure of the le- obtaining wide tumor-free margins nerve root). Total sacrectomy is per- sions often requires a staged operation when possible cannot be underesti- formed when both S1 nerve roots in which standard anterior, posterior, mated. Numerous studies demon- must be sacrificed.23 perineal, and lateral approaches are

712 Journal of the American Academy of Orthopaedic Surgeons Daniel M. Sciubba, MD, et al used in combination. Following tumor region with complex anatomy and Figure 6 excision, advanced techniques in instru- many sensitive structures. These tumors mentation (eg, iliac screws, transiliac may extend into the retropharyngeal bars) may be required to prevent space or may spread epidurally, caus- spinopelvic instability, particularly for ing spinal cord compression. Multidis- patients who require high amputation ciplinary teams may be involved, in- or total sacrectomy31 (Figure 6). In cluding ear, nose, and throat specialists addition, soft-tissue reconstruction and plastic surgeons. The anterior phase with rotational gluteal flaps or of these procedures often consists of transpelvic vertical rectus abdominis transglossal or transmandibular ap- myocutaneous flaps is recommended proaches (as opposed to transoral ap- to promote wound healing and oblit- proaches). These approaches provide erate dead space.23 adequate visualization of the tumor For vertebral body chordomas, en pseudocapsule and allow for extracap- bloc resection with tumor-free margins sular excision (Figure 8). Instrumenta- remains the goal of surgical treatment. tion is necessary to achieve clival- Numerous studies have demonstrated cervical stability, and tracheostomy and that intralesional excision leads to a percutaneous endoscopic gastrostomy high rate of local recurrence and neg- are generally performed prophylacti- atively affects overall survival.3,4 To cally. Complications include those that avoid this, en bloc spondylectomy, or result from damage to nearby neuro- removal of the entire vertebral body logic structures, such as dysphagia, dys- Plain AP radiograph following sacral tumor resection and in one block, is performed (Figure 7). phonia, Horner syndrome, and hypo- instrumentation. Pedicle screws This procedure often requires a com- glossal nerve injury. were placed in the lumbar bination of posterior and anterior Radiation therapy can be used as vertebrae bilaterally and connected via rods to iliac screws and approaches, including thoracoab- an adjuvant treatment for chordo- transiliac bolts, allowing dominal and retroperitoneal abdomi- mas with incomplete resection or reconstruction of the lumbopelvic nal as well as transpleural thoracoto- positive margins; however, the effi- junction. my).25 En bloc removal of all cacy of such treatment is unproved. posterior elements of the vertebra is Their proximity to sensitive neuro- performed, followed by en bloc re- logic tissues make chordomas diffi- sults given the rarity of the disease as section of the anterior portion. Spi- cult to treat with standard radiation well as the variability in surgical pro- nal reconstruction is necessary. Ex- therapy.35 These tumors are relatively cedure, completeness of excision, and cellent results have been obtained radiation-resistant and thus are the timing and method of delivery of ra- with these surgical techniques.32-34 thought to require doses of ≥60 to diotherapy. However, radiation treat- Wide en bloc resection is not al- 70 Gy, which may surpass the doses ments are improving with recent ways possible, either because of the safely tolerated by the spinal cord.35 advances in photon-beam therapy, in- size or extent of the tumor or be- Moreover, metal hardware associ- cluding the use of intensity-modulated cause such resection would lead to ated with spinal reconstructive sur- radiation therapy and stereotactic ra- excessive morbidity. Even though the gery may produce artifacts that inter- diosurgery. Improved accuracy of tu- margins are intralesional in these fere with accurate targeting of the mor targeting can be achieved with cases, an effort is made to perform tumor volume during radiation ther- both of these techniques, allowing for extracapsular excision of the chor- apy.35 Conventional photon-beam an increased tumor dose with reduced doma, which involves removal of the radiation therapy is used as an adju- collateral damage to surrounding specimen without penetration of its vant treatment in patients undergo- tissues.27,37 The use of radiosensitiz- surrounding pseudocapsule.4 Often ing subtotal excision. However, re- ing agents to enhance response to these patients then receive adjuvant ports vary as to whether additional photon-beam therapy has been re- radiation therapy to provide local survival benefit is derived.36 Conven- ported in a small number of pa- control over any residual disease.27 tional treatments with doses of 40 to tients.38 Chordomas in the upper cervical ver- 60 Gy have produced 5-year local Hadron therapy, which makes use tebrae require special consideration. control rates of 10% to 40%.35 of protons or charged particles such Like sacral chordomas, these are in a It is difficult to interpret and apply re- as carbon ions, helium, and neon, is

November 2009, Vol 17, No 11 713 Chordoma of the Sacrum and Vertebral Bodies

Figure 7

A, T2-weighted sagittal MRI scan of an L1 chordoma (arrow) that was treated via a two-stage operation. First, the posterior elements were removed radically, and instrumentation was placed. Next, an anterior, retroperitoneal approach was used to complete the vertebrectomy and to allow placement of a vertebral body replacement device (ie, titanium cage). Lateral (B) and AP (C) three-dimensional reconstructed CT images demonstrating the ﬁnal construct.

another promising treatment modal- fer an improvement in chordoma geted agents has led to renewed ity for chordomas. Because of the treatment, with reported local con- interest in the use of chemotherapy. ballistic properties of these particles, trol rates of 50% to 60% at 5 One such agent, imatinib, an inhibi- hadron dose deposition is limited to years.41 However, there is no level I tor of platelet-derived growth factor a sharply defined Bragg peak, which or II evidence to support this. receptor-β (PDGFR-β), was used to provides a steep gradient between Most of these studies are smaller treat chordomas in 18 patients.43 the target dose and that delivered to case series, and they often combine Many of these patients demonstrated the surrounding tissues.35 Thus, had- data related to patients with chon- symptomatic improvement and a tu- ron therapy permits delivery of high- drosarcoma and those with chor- mor response evidenced by a reduc- dose radiation to the target tissue doma. More data are needed to eval- tion in contrast enhancement, with that, in principle, could surpass even uate the true short- and long-term effects lasting for 1 year. These re- the most sophisticated photon radia- efficacy of hadron therapy and to sults are promising, especially in tion delivery techniques while mini- better determine the scenarios in light of the recent report of a series mizing damage to nearby sensitive which it will be useful as an adjunct of 31 chordomas, all of which dis- structures.39 Additionally, certain had- treatment for chordoma. played overexpression and activation ron particle beams may offer supe- Chordomas have proved to be of PDGFR-β.44 Clinical trials are rior tumor kill properties.40 Hadron highly resistant to chemotherapy. ongoing, and other drugs are under therapy may be used in combination This modality may have some impact investigation for chordoma, includ- with conventional photon beam ther- on the rare, high-grade dedifferenti- ing antiangiogenic agents and epider- apy, or it may be given alone.35 ated chordoma.42 However, the de- mal growth factor receptor inhibi- Proton-beam therapy appears to of- velopment of newer molecularly tar- tors.35

714 Journal of the American Academy of Orthopaedic Surgeons Daniel M. Sciubba, MD, et al

Prognosis Figure 8

Current studies suggest that the prognosis for patients with chordoma has improved dramatically with the adoption of aggressive surgical treatments.2-4 Older studies reported 5-year survival rates of 50% to 68% and 10-year survival rates of 28% to 40%,2,4 whereas newer case series report 5-year survival rates of 73% to 86% and 10-year survival rates of 49% to 71%.3-5 Although chordomas are considered to be slow-growing neoplasms, they do have the propensity to metastasize. Me- tastases have been found in up to 5% of patients at the time of diagnosis and in up to 65% at autopsy; the most common sites of metastasis are the lungs, soft tissues, bone, skin, pancreas, heart, and brain.5,22 Most surgeons agree, however, that local recurrence is the most important determinant of long-term survival and that local control is the key to successful treatment.3,4,45 Bergh et al3 report a 21-fold increase in risk of tumor-related death in those with recurrent local disease. Several studies have confirmed that the recurrence rate is greatly increased for patients with intralesional excision compared with those who had ade- 3,36,46 T2-weighted axial (A) and T1-weighted sagittal (B) MRI scans of a cervical quate margins. Local control is chordoma (arrows). Use of a posterolateral approach allowed simultaneous difficult to achieve without en bloc resection and placement of posterior instrumentation. C, Intraoperative excision and tumor-free margins re- photograph. D, Scout ﬁlm from CT scan. gardless of the use of adjuvant radiotherapy.4,5 Thus, the current standard of care for chordomas remains ag- release from the hospital, surveil- sponsive to radiation and chemother- gressive en bloc surgical resection lance MRI scans are obtained every apy; thus, surgical resection remains whenever possible to achieve optimal 3 months in the first year following the mainstay of treatment. Local local control and survival. resection, every 6 months in the sec- control and overall survival have With the high rate of recurrence ond year, and annually thereafter. been linked with the ability to per- and the resulting poor prognosis, ex- form radical resection. However, tended follow-up and surveillance is Summary given the propensity for such lesions necessary for chordoma patients. At to become intimately associated with our institution, patients undergo CT Chordomas can appear at any loca- neural, vascular, and visceral struc- scan of the resection bed immedi- tion along the spine and often show tures, specifically at the skull base ately postoperatively, and MRI scan- advanced growth at the time of diag- and sacrum, surgical morbidity may ning is done within 48 hours. After nosis. Such tumors are minimally re- be substantial. For this reason, treat-

November 2009, Vol 17, No 11 715 Chordoma of the Sacrum and Vertebral Bodies ment of patients with chordomas 8. Murphey MD, Andrews CL, Flemming 22. Boriani S, Chevalley F, Weinstein JN, should involve a multidisciplinary DJ, Temple HT, Smith WS, et al: Chordoma of the spine above the Smirniotopoulos JG: From the archives sacrum: Treatment and outcome in 21 team consisting of doctors in the of the AFIP: Primary tumors of the spine. cases. Spine (Phila Pa 1976) 1996;21: fields of surgical oncology, radiation Radiologic pathologic correlation. 1569-1577. Radiographics 1996;16:1131-1158. oncology, neurosurgery, orthopaedic 23. Fourney DR, Rhines LD, Hentschel SJ, surgery, general surgery, and plastic 9. Llauger J, Palmer J, Amores S, Bagué S, et al: En bloc resection of primary sacral Camins A: Primary tumors of the tumors: Classification of surgical surgery, as needed, to provide the sacrum: Diagnostic imaging. AJR Am J approaches and outcome. J Neurosurg best chance for an optimal outcome. Roentgenol 2000;174:417-424. Spine 2005;3:111-122. 10. Maclean FM, Soo MY, Ng T: 24. Murphy JM, Wallis F, Toland J, Toner Chordoma: Radiological-pathological M, Wilson GF: CT and MRI References correlation. Australas Radiol 2005;49: appearances of a thoracic chordoma. Eur 261-268. Radiol 1998;8:1677-1679.

Evidence-based Medicine: Levels of 11. Sciubba DM, Chi JH, Rhines LD, 25. Boriani S, Weinstein JN, Biagini R: Gokaslan ZL: Chordoma of the spinal Primary bone tumors of the spine: evidence are described in the table of column. Neurosurg Clin N Am 2008;19: Terminology and surgical staging. Spine contents. In this article, no level I or II 5-15. (Phila Pa 1976) 1997;22:1036-1044. studies are cited. References 2 and 26 12. Hanna SA, Tirabosco R, Amin A, et al: 26. Chan P, Boriani S, Fourney DR, et al: An Dedifferentiated chordoma: A report of assessment of the reliability of the are level III studies. Level IV studies four cases arising ‘de novo’. J Bone Joint Enneking and Weinstein-Boriani-Biagini include references 3-5, 12, 14, 19-22, Surg Br 2008;90:652-656. classifications for staging of primary spinal tumors by the Spine Oncology 25, 27, 28, 32, 33, 36-38, 41, and 13. Yamaguchi T, Suzuki S, Ishiiwa H, Ueda Study Group. Spine (Phila Pa 1976) 43-45. References 1, 6-11, 13, 15- Y: Intraosseous benign notochordal cell 2009;34:384-391. tumours: Overlooked precursors of 18, 23, 24, 29-31, 34, 35, 39, 40, classic chordomas? Histopathology 27. Bilsky MH, Yamada Y, Yenice KM, et al: 42, and 46 are level V studies. 2004;44:597-602. Intensity-modulated stereotactic radiotherapy of paraspinal tumors: A Citation numbers printed in bold 14. Yamaguchi T, Suzuki S, Ishiiwa H, preliminary report. Neurosurgery 2004; Shimizu K, Ueda Y: Benign notochordal 54:823-830. type indicate references published cell tumors: A comparative histological within the past 5 years. study of benign notochordal cell tumors, 28. Todd LT Jr, Yaszemski MJ, Currier BL, classic chordomas, and notochordal Fuchs B, Kim CW, Sim FH: Bowel and 1. Healey JH, Lane JM: Chordoma: A vestiges of fetal intervertebral discs. Am J bladder function after major sacral Surg Pathol 2004;28:756-761. resection. Clin Orthop Relat Res 2002; critical review of diagnosis and 397:36-39. treatment. Orthop Clin North Am 1989; 15. Greenspan A, Jundt G, Remagen W: 20:417-426. Chordoma, in Differential Diagnosis in 29. Biagini R, Ruggieri P, Mercuri M, et al: Orthopaedic Oncology,ed2. Neurologic deficit after resection of the 2. McMaster ML, Goldstein AM, Bromley Philadelphia, PA, Lippincott Williams & sacrum. Chir Organi Mov 1997;82:357- CM, Ishibe N, Parry DM: Chordoma: Wilkins, 2006, pp 445-446. 372. Incidence and survival patterns in the United States, 1973-1995. Cancer 16. Yamaguchi T, Iwata J, Sugihara S, et al: 30. Stener B, Gunterberg B: High Causes Control 2001;12:1-11. Distinguishing benign notochordal cell amputation of the sacrum for extirpation tumors from vertebral chordoma. of tumors: Principles and technique. 3. Bergh P, Kindblom LG, Gunterberg B, Skeletal Radiol 2008;37:291-299. Spine (Phila Pa 1976) 1978;3:351-366. Remotti F, Ryd W, Meis-Kindblom JM: Prognostic factors in chordoma of the 17. Heary RF, Vaccaro AR, Benevenia J, 31. Jackson RJ, Gokaslan ZL: Spinal-pelvic sacrum and mobile spine: A study of 39 Cotler JM: “En-bloc” vertebrectomy in fixation in patients with lumbosacral patients. Cancer 2000;88:2122-2134. the mobile lumbar spine. Surg Neurol neoplasms. J Neurosurg 2000;92(1 1998;50:548-556. suppl):61-70. 4. Boriani S, Bandiera S, Biagini R, et al: Chordoma of the mobile spine: Fifty 18. Estrozi B, Queiroga E, Bacchi CE, et al: 32. Hsu KY, Zucherman JF, Mortensen N, years of experience. Spine (Phila Pa Myxopapillary ependymoma of the Johnston JO, Gartland J: Follow-up 1976) 2006;31:493-503. posterior mediastinum. Ann Diagn evaluation of resected lumbar vertebral Pathol 2006;10:283-287. chordoma over 11 years: A case report. 5. Cheng EY, Ozerdemoglu RA, Transfeldt Spine (Phila Pa 1976) 2000;25:2537- EE, Thompson RC Jr: Lumbosacral 19. Enneking WF, Spanier SS, Goodman 2540. chordoma: Prognostic factors and MA: A system for the surgical staging of treatment. Spine (Phila Pa 1976) 1999; musculoskeletal sarcoma. Clin Orthop 33. Sundaresan N, Steinberger AA, Moore F, 24:1639-1645. Relat Res 1980;153:106-120. et al: Indications and results of combined anterior-posterior approaches for spine 6. Singh N, Soo M, De Cruz M, Gomes L, 20. Enneking WF: A system of staging tumor surgery. J Neurosurg 1996;85: Maclean F, Dandie G: Cervical musculoskeletal neoplasms. Clin Orthop 438-446. chordoma presenting as retropharyngeal Relat Res 1986;204:9-24. mass and dysphonia: Case report and 34. Tomita K, Kawahara N, Murakami H, literature review. Australas Radiol 2007; 21. Hart RA, Boriani S, Biagini R, Currier B, Demura S: Total en bloc spondylectomy 51(suppl):B183-B188. Weinstein JN: A system for surgical for spinal tumors: Improvement of the staging and management of spine technique and its associated basic 7. Fourney DR, Gokaslan ZL: Current tumors: A clinical outcome study of background. J Orthop Sci 2006;11:3-12. management of sacral chordoma. giant cell tumors of the spine. Spine Neurosurg Focus 2003;15:E9. (Phila Pa 1976) 1997;22:1773-1782. 35. Casali PG, Stacchiotti S, Sangalli C,

716 Journal of the American Academy of Orthopaedic Surgeons Daniel M. Sciubba, MD, et al

Olmi P, Gronchi A: Chordoma. Curr 40. Welsh JS: Basics of particle therapy: 44. Tamborini E, Miselli F, Negri T, et al: Opin Oncol 2007;19:367-370. Introduction to hadrons. Am J Clin Molecular and biochemical analyses of Oncol 2008;31:493-495. platelet-derived growth factor receptor 36. York JE, Kaczaraj A, Abi-Said D, et al: (PDGFR) B, PDGFRA, and KIT Sacral chordoma: 40-year experience at a 41. Nöel G, Feuvret L, Calugaru V, et al: receptors in chordomas. Clin Cancer Res major cancer center. Neurosurgery 1999; Chordomas of the base of the skull and 2006;12:6920-6928. 44:74-79. upper cervical spine: One hundred patients irradiated by a 3D conformal 45. Hulen CA, Temple HT, Fox WP, Sama 37. Jereczek-Fossa BA, Krengli M, Orecchia technique combining photon and proton AA, Green BA, Eismont FJ: Oncologic R: Particle beam radiotherapy for head beams. Acta Oncol 2005;44:700-708. and functional outcome following and neck tumors: Radiobiological basis sacrectomy for sacral chordoma. J Bone and clinical experience. Head Neck 42. Fleming GF, Heimann PS, Stephens JK, Joint Surg Am 2006;88:1532-1539. 2006;28:750-760. et al: Dedifferentiated chordoma: Response to aggressive chemotherapy in 46. Hanna SA, Aston WJ, Briggs TW, 38. Rhomberg W, Eiter H, Böhler F, two cases. Cancer 1993;72:714-718. Cannon SR, Saifuddin A: Sacral Dertinger S: Combined radiotherapy and chordoma: Can local recurrence after razoxane in the treatment of 43. Casali PG, Stacchiotti S, Messina A, sacrectomy be predicted? Clin Orthop chondrosarcomas and chordomas. et al: Imatinib mesylate in 18 advanced Relat Res 2008;466:2217-2223. Anticancer Res 2006;26:2407-2411. chordoma patients. J Clin Oncol 2005; 23:9012. 39. Suit H, Goldberg S, Niemierko A, et al: Proton beams to replace photon beams in radical dose treatments. Acta Oncol 2003;42:800-808.

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